Schedule H

Oral

• Tablets: 2 mg, 4 mg, 8 mg (as perindopril erbumine or perindopril arginine)

Note: Perindopril erbumine and perindopril arginine are not dose-equivalent. Perindopril arginine 2.5 mg ≈ Perindopril erbumine 2 mg; Perindopril arginine 5 mg ≈ Perindopril erbumine 4 mg; Perindopril arginine 10 mg ≈ Perindopril erbumine 8 mg. Most Indian formulations are perindopril erbumine.

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India):

1. Essential Hypertension

Parameter Dose Clinical Notes

Starting dose 4 mg orally once daily (morning) If on diuretics, volume-depleted, or elderly: start at 2 mg once daily

Titration Increase after 2–4 weeks based on BP response

Usual maintenance dose 4–8 mg once daily

Maximum dose 8 mg/day

Note: First-dose hypotension risk in volume-depleted patients; consider withholding diuretic for 2–3 days before initiation or starting at 2 mg.

1. Stable Coronary Artery Disease (Secondary Prevention)

Parameter Dose Clinical Notes

Starting dose 4 mg orally once daily For 2 weeks

Titration Increase to 8 mg once daily if tolerated After 2 weeks

Usual maintenance dose 8 mg once daily

Maximum dose 8 mg/day

Clinical Note: EUROPA trial demonstrated reduced cardiovascular events in stable CAD patients without heart failure. Widely used in Indian cardiology practice for secondary prevention.

1. Heart Failure with Reduced Ejection Fraction (HFrEF)

Parameter Dose Clinical Notes

Starting dose 2 mg orally once daily Start lower if hypotensive or on high-dose diuretics

Titration Double dose every 1–2 weeks as tolerated Monitor BP, renal function, potassium

Usual maintenance dose 4–8 mg once daily Target maximum tolerated dose

Maximum dose 8 mg/day

Used as part of guideline-directed medical therapy (GDMT) with beta-blockers, diuretics, and mineralocorticoid receptor antagonists.

1. Post-Myocardial Infarction (Early Treatment — within 24–48 hours if haemodynamically stable)

Parameter Dose Clinical Notes

Starting dose 2 mg orally once daily Initiate if systolic BP ≥100 mmHg and no contraindications

Titration Increase to 4 mg once daily after 2 days, then 8 mg once daily after further 2 days Based on tolerance

Usual maintenance dose 8 mg once daily

Maximum dose 8 mg/day

Secondary Indications — Adults (Off-label, if any)

1. Diabetic Nephropathy with Proteinuria — OFF-LABEL

Parameter Details

Indication Type 1 or Type 2 diabetes with albuminuria/proteinuria for renal protection

Dose 4–8 mg once daily

Duration Long-term

Specialist only Yes — Nephrology for CKD Stage 3 or worse

Evidence basis Class effect of ACE inhibitors for renoprotection; ADVANCE trial (perindopril-based); Indian nephrology practice

1. Non-Diabetic Chronic Kidney Disease with Proteinuria — OFF-LABEL

Parameter Details

Indication Proteinuric CKD for slowing disease progression

Dose 4–8 mg once daily; start 2 mg if eGFR <30

Duration Long-term

Specialist only Yes — Nephrology

Evidence basis Class effect; Indian nephrology practice

PAEDIATRIC DOSING (Specialist Only)

Primary Indications:

NOT APPROVED for paediatric use in India.

• Safety and efficacy in children and adolescents below 18 years have not been established

• No weight-based dosing standardised in Indian guidelines

• No paediatric formulation marketed in India

Secondary Indications — Paediatrics (Off-label, if any)

Not applicable.

Not recommended below 18 years of age. If use is considered essential in exceptional circumstances (e.g., refractory hypertension, heart failure in adolescents), it should be under specialist paediatric nephrology or cardiology supervision with individualised dosing extrapolated from adult data and close monitoring.

60 Standard starting dose 8 mg/day Monitor renal function and potassium

30–60 2 mg once daily 4 mg/day Titrate cautiously; close monitoring essential

15–30 2 mg once daily 2 mg/day Use with caution; consider alternative ACE inhibitors with more data

<15 (non-dialysis) 2 mg on alternate days 2 mg/day Avoid if possible; specialist supervision

Haemodialysis 2 mg on dialysis days 2 mg on dialysis days Administer after dialysis (perindoprilat is partially dialyzable)

Peritoneal dialysis 2 mg once daily 2 mg/day Limited data; use with caution

Key Points:

• Monitor serum creatinine and potassium within 1–2 weeks of initiation and after dose changes

• Expect mild rise in creatinine (up to 30% from baseline) initially; >30% rise requires investigation

• Contraindicated in bilateral renal artery stenosis

• Known hypersensitivity to perindopril or any other ACE inhibitor

• History of angioedema associated with previous ACE inhibitor therapy

• Hereditary or idiopathic angioedema

• Bilateral renal artery stenosis or stenosis of artery to a solitary kidney

• Pregnancy (all trimesters — fetotoxic)

• Concurrent use with aliskiren in patients with diabetes mellitus or eGFR <60 mL/min/1.73m²

• Concurrent use with sacubitril/valsartan (ARNI) — minimum 36-hour washout required before switching

• Volume depletion or salt depletion (risk of severe first-dose hypotension)

• Pre-existing renal impairment (monitor renal function and potassium closely)

• Renovascular disease (risk of acute renal failure)

• Aortic stenosis or hypertrophic obstructive cardiomyopathy (may not tolerate afterload reduction)

• Hyperkalaemia or concurrent potassium-sparing diuretics/potassium supplements

• Collagen vascular diseases (SLE, scleroderma) — increased risk of neutropenia

• Elderly patients (increased sensitivity to hypotensive effects and renal impairment)

• Black patients (may have reduced response; higher angioedema risk)

• Major surgery/anaesthesia (may cause hypotension under anaesthesia)

• Haemodialysis with high-flux polyacrylonitrile membranes (increased anaphylactoid reaction risk)

Aspect Recommendation

Risk category Contraindicated in all trimesters

First trimester Avoid; associated with cardiovascular and CNS malformations (conflicting data but precautionary avoidance recommended)

Second/Third trimester Absolutely contraindicated — causes fetal renal dysgenesis, oligohydramnios, pulmonary hypoplasia, skeletal deformities, neonatal renal failure, hypotension, death

Preferred alternatives Labetalol, methyldopa, nifedipine (per Indian obstetric guidelines)

If exposure occurred Immediate specialist referral; detailed fetal ultrasound for renal anomalies, oligohydramnios, growth restriction

Monitoring Fetal growth, amniotic fluid volume; neonatal renal function and blood pressure if born after exposure

Aspect Recommendation

Compatibility Not recommended; limited data available

Drug levels in milk Small amounts of perindopril may pass into breast milk

Preferred alternatives Enalapril or captopril (more safety data in lactation); methyldopa; labetalol

Recommendations Avoid if possible during breastfeeding; if essential, use with caution

Infant monitoring Lethargy, poor feeding, hypotension, adequate weight gain

Aspect Recommendation

Starting dose 2 mg once daily

Titration Slow titration; increase at 2–4 week intervals based on tolerance

Special considerations Age-related decline in renal function common; calculate/estimate eGFR before dosing

Extra risks First-dose hypotension; orthostatic hypotension leading to falls; hyperkalaemia; acute kidney injury

Monitoring Blood pressure (including orthostatic); renal function; serum potassium within 1–2 weeks of initiation

Drug Interaction Management

Potassium-sparing diuretics (spironolactone, amiloride, eplerenone) Severe hyperkalaemia Avoid in renal impairment; if combined (e.g., in HFrEF), monitor potassium closely within 1 week and regularly thereafter

Potassium supplements Hyperkalaemia Avoid unless documented hypokalaemia; monitor potassium

Lithium Increased lithium levels → toxicity Avoid combination if possible; if essential, monitor lithium levels closely and consider dose reduction

Aliskiren Increased risk of hyperkalaemia, hypotension, and renal impairment Contraindicated in diabetes or eGFR <60 mL/min/1.73m²; avoid in all patients if possible

Sacubitril/Valsartan (ARNI) Increased angioedema risk Do not co-administer; 36-hour washout required before switching

ARBs (dual RAAS blockade) Increased renal impairment, hyperkalaemia, hypotension without additional benefit Avoid combination except under specialist supervision

NSAIDs (chronic use) Reduced antihypertensive effect; increased renal impairment risk; hyperkalaemia Avoid prolonged concurrent use; if necessary, monitor BP, renal function, and potassium

Drug Interaction Management

Thiazide diuretics Enhanced hypotensive effect; first-dose hypotension Start perindopril at lower dose (2 mg) or temporarily hold diuretic

Loop diuretics (furosemide) Enhanced hypotensive effect Monitor BP and volume status; start perindopril at lower dose

Antidiabetic agents (insulin, sulfonylureas) Enhanced hypoglycaemic effect Monitor blood glucose, especially in first weeks

Trimethoprim / Co-trimoxazole Additive hyperkalaemia risk Monitor potassium within 1 week of starting combination

Allopurinol Increased risk of hypersensitivity reactions and leucopenia Monitor; use with caution

Baclofen Enhanced hypotensive effect Monitor blood pressure

Anaesthetic agents Enhanced hypotension Inform anaesthetist; may need to hold on day of surgery

Gold (sodium aurothiomalate) Nitritoid reactions (flushing, nausea, hypotension) Monitor during gold injections

• Dry persistent cough (5–15%) — class effect; due to bradykinin accumulation

• Dizziness

• Headache

• Fatigue and asthenia

• Hypotension (especially first-dose)

• Nausea, abdominal pain

• Diarrhoea

• Rash and pruritus

• Hyperkalaemia

• Elevated serum creatinine (usually transient)

Adverse Effect Clinical Notes

Angioedema Face, lips, tongue, larynx, intestine; may be life-threatening; discontinue immediately; do not rechallenge with any ACE inhibitor; higher risk in Black patients

Severe hypotension Especially first-dose in volume-depleted patients; may cause syncope; may require IV fluids

Acute kidney injury Particularly in bilateral renal artery stenosis or severe heart failure; monitor creatinine

Hyperkalaemia (severe) Can cause cardiac arrhythmias; more common with renal impairment or concurrent potassium-sparing agents

Neutropenia / Agranulocytosis Rare; more common in collagen vascular diseases or renal impairment; discontinue if WBC falls significantly

Hepatotoxicity Rare; cholestatic jaundice, hepatic failure reported; discontinue if occurs

Stevens-Johnson Syndrome / TEN Very rare; discontinue immediately

Foetotoxicity Severe fetal harm in pregnancy — contraindicated

Action: Discontinue perindopril immediately if angioedema, severe hyperkalaemia, significant renal deterioration, or hypersensitivity reactions occur.

After initiation/dose change BP, serum creatinine, and potassium within 1–2 weeks; earlier (3–5 days) if high-risk (elderly, renal impairment, heart failure on diuretics)

During stable therapy BP at each visit; serum creatinine and potassium every 3–6 months; more frequently if renal impairment or concurrent potassium-affecting drugs

Long-term Annual renal function assessment; reassess indication and response; monitor for persistent cough and angioedema symptoms

Acceptable creatinine rise: Up to 30% increase from baseline is acceptable; if >30% or progressive, investigate for renovascular disease or withhold/reduce dose.

• Coversyl (Serdia/Servier) — originator brand

• Covance (Abbott)

• Perigard (Eris)

• Perindil (Micro Labs)

• Perindo (Cipla)

• Multiple generic manufacturers

• Not listed in NLEM 2022

• Not under NPPA price control

• Higher cost compared to enalapril; used when specific indication (stable CAD) or once-daily convenience preferred

1. Once-daily convenience — perindopril has a long half-life allowing true once-daily dosing with consistent 24-hour BP control; preferred when compliance is a concern.

1. EUROPA trial evidence — perindopril has specific RCT evidence (EUROPA) for reducing cardiovascular events in stable CAD without heart failure; consider for secondary prevention in this population.

1. Dry cough incidence — some data suggest slightly lower cough incidence compared to enalapril, though this remains patient-specific; if cough occurs, switch to ARB rather than another ACE inhibitor.

1. Prodrug metabolism — perindopril is a prodrug converted to active perindoprilat by hepatic esterases; in severe hepatic impairment, consider lisinopril (not a prodrug) as alternative.

1. First-dose hypotension prevention — in patients on diuretics or volume-depleted, start at 2 mg once daily; consider giving first dose at bedtime to minimise symptomatic hypotension.

1. Check renal function and potassium early — monitor within 1–2 weeks of initiation or dose change; accept up to 30% rise in creatinine as expected; >30% rise requires investigation.

1. 36-hour washout for ARNI switch — if switching from perindopril to sacubitril/valsartan, wait minimum 36 hours to reduce angioedema risk.

perindopril; ACE inhibitor; hypertension; stable CAD; coronary artery disease; heart failure; HFrEF; EUROPA trial; secondary prevention; pregnancy-contraindicated; renal-adjust; Schedule H

RxIndia v1.0 — 09 May 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia

• API Textbook of Medicine

• ICMR Hypertension Guidelines

• Cardiological Society of India (CSI) Guidelines

• AIIMS Internal Medicine Protocols

• EUROPA Trial (Lancet 2003 — for stable CAD indication)

• ADVANCE Trial (Lancet 2007 — for diabetes/perindopril-based regimen)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (supportive)